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Selective tau tyrosine nitration in non-AD tauopathies

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Abstract

Previously, we reported the characterization of two novel antibodies that react with tau nitrated at tyrosine 197 (Tau-nY197) and tyrosine 394 (Tau-nY394) in Alzheimer’s disease (AD). In this report, we examined whether tau nitration at these sites also occurs in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick’s disease (PiD), three neurodegenerative tauopathies that contain abundant tau deposits within glial and neuronal cell types but lack amyloid deposition. The reactivity of these antibodies was also compared to two previously characterized antibodies Tau-nY18 and Tau-nY29, specific for tau nitrated at tyrosine 18 and tyrosine 29, respectively. In the present experiments, Tau-nY18 did not label the classical pathological lesions of CBD or PSP but did label the neuronal lesions associated with PiD to a limited extent. In contrast, Tau-nY29 revealed some, but not all classes of tau inclusions associated with both CBD and PSP but did label numerous Pick body inclusions in PiD. Tau-nY197 was restricted to the neuropil threads in both CBD and PSP; however, similar to Tau-nY29, extensive Pick body pathology was clearly labeled. Tau-nY394 did not detect any of the lesions associated with these disorders. In contrast, extensive neuronal and glial tau pathology within these diseases was labeled by Tau-Y197, a monoclonal antibody that reacts within the Y-197-containing proline-rich region of the molecule. Based on our Western and IHC experiments, it appears that nitration of tau at tyrosine 29 is a pathological modification that might be associated with neurodegeneration. Collectively, our data suggest that site-specific tau tyrosine nitration events occur in a disease and lesion-specific manner, indicating that nitration appears to be a highly controlled modification in AD and non-AD tauopathies.

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Acknowledgments

The authors would like thank Katherine Gasho and Dr. Eileen Bigio from the CNADC of Northwestern University for kindly providing the tissue necessary to complete this study. We are grateful to Dr. Rohan de Silva for kindly providing us with the RD3 and RD4 antibodies and Dr. Sarah Ward for critical readings of the manuscript. This work is supported by NIH awards AG 14449 (L.I.B.), AG 21184 (L.I.B.), AG 032091 and AG 013854 to the Northwestern University Alzheimer’s Disease Center (C.G.).

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Juan F. Reyes, Laurel Vana & Lester I. Binder

  2. Cognitive Neurology and Alzheimer’s Disease Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Changiz Geula & Lester I. Binder

  3. Tarry Bldg. 8-754, 300 E. Superior St., Chicago, IL, 60611, USA

    Juan F. Reyes

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  1. Juan F. Reyes
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Correspondence to Juan F. Reyes.

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Reyes, J.F., Geula, C., Vana, L. et al. Selective tau tyrosine nitration in non-AD tauopathies. Acta Neuropathol 123, 119–132 (2012). https://doi.org/10.1007/s00401-011-0898-8

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  • DOI: https://doi.org/10.1007/s00401-011-0898-8

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